Hepatocellular Carcinoma

NORD gratefully acknowledges Jonathan M. Schwartz, MD, Professor of Clinical Medicine, Division of Gastroenterology and Liver Diseases, Albert Einstein College of Medicine, Montefiore Medical Center, for assistance in the preparation of this report.

Synonyms of Hepatocellular Carcinoma

HCC

malignant hepatoma

General Discussion

Summary

Hepatocellular carcinoma (HCC) is a rare disorder in the United States, but the most common primary tumor of the liver. Most people have an underlying liver disease such as infection with hepatitis B or C virus, or non-alcoholic fatty liver disease. Most people have cirrhosis, which is scarring of the liver that can occur as a result of chronic liver diseases. If HCC is found early, there may be curative treatments offered. However, HCC often does not cause any symptoms, especially early in the disease course. If HCC is diagnosed at a late stage, patients may not be able to receive curative treatments, and care is then geared toward helping people have a better quality of life. Although HCC does not necessarily cause symptoms, many individuals will have symptoms caused by the underlying liver disease. The exact cause of HCC is not fully understood.

Signs & Symptoms

Most people do not have any noticeable symptoms associated with hepatocellular carcinoma. They may have symptoms related liver cirrhosis that may become more difficult to control.

Because of the underlying liver disease and HCC, the liver may become decompensated. This means that an organ, in this instance the liver, is having trouble compensating for the effects of disease. Symptoms of liver decompensation can include fluid buildup in the abdomen (ascites), an abnormally enlarged spleen (splenomegaly), high pressure in the main vein that supplies the liver (portal hypertension), yellowing of the skin, eyes and mucous membranes because of the buildup of bile in the body (jaundice), and hepatic encephalopathy, a condition in which toxins that are normally cleared by the liver are not cleared and instead travel through the bloodstream to the brain. Hepatic encephalopathy is a spectrum of disease that can cause very subtle symptoms or severe, life-threatening complications. When symptoms do occur, they can include personality changes, intellectual impairment, impaired memory or loss of consciousness (coma).

Although HCC often does not cause symptoms, some people will develop mild to moderate pain in the upper abdomen and may feel full despite eating less food than usual (early satiety). Some may experience fatigue, unintended weight loss or have a mass that can be felt (palpable) in the upper abdomen. Less commonly, fever or diarrhea may be present. Usually, such symptoms occur later in the diseases course and indicate advanced disease.

Some symptoms may occur if the cancer has spread to other areas (metastasized). For example, bone pain may occur if the cancer has spread to the bones, or a person may have difficulty breathing (dyspnea) if the cancer has spread to the lungs.

Some people with HCC may develop a paraneoplastic syndrome. Paraneoplastic syndromes are a group of disorders that occur when the immune system’s response to cancer also damages the central nervous system.

There is also a risk of a tumor rupturing, leading to bleeding into the peritoneum, which is the membrane that lines the abdomen and covers the abdominal organs (intraperitoneal hemorrhage).

Causes

The exact reasons why hepatocellular carcinoma develops is not fully understood. It is a multifactorial disorder, which means that there are multiple factors that must occur before the disorder develops.

There are risk factors that increase the chances of a person developing HCC. Most people have an underlying liver disorder including infection with hepatitis B or C viruses, scarring of the liver (cirrhosis), a condition in which fat builds up in the liver (non-alcoholic fatty liver disease), and a condition in which fat builds up in the liver along with inflammation and liver cell damage (nonalcoholic steatohepatitis or NASH). Heavy drinking is also a risk factor for HCC; excessive drinking is one of the main causes of cirrhosis and can also cause alcoholic fatty liver disease. Cigarette smoking is also a potential risk factor for HCC.

Obesity and diabetes are modest risk factors, but the absolute risk is considered to be very low. Foods contaminated with aflatoxin also increase the risk of HCC; this is even true for people without an underlying liver disorder. Aflatoxins are a type of toxin produced by fungi and may contaminate certain agricultural products.

There are also several metabolic and genetic disorders that may increase the risk of developing HCC. These disorders include Wilson disease, hemochromatosis, autoimmune hepatitis, alpha-1 antitrypsin deficiency, and primary biliary cholangitis (For more information on these disorders, choose the specific disorder name as your search term in the NORD Rare Disease Database.).

Affected Populations

Hepatocellular carcinoma is one of the most prevalent cancers in the world, but relatively rare in the United States. There are approximately six new cases of HCC per every 100,000 people in the general population of the U.S. The number of people who develop HCC in the U.S. has risen in the last four decades. In certain geographic regions in the world, HCC is much more common most likely due to increased frequency of hepatitis B infection or exposure to aflatoxins. One estimate places HCC as the fifth most common cancer that leads to death in the world.

HCC accounts for about 85%-90% of all primary liver cancers. Primary means that the cancer started in the liver as opposed to secondary, in which cancer has spread to the liver from another area of the body.

Related Disorders

Symptoms of the following disorders can be similar to those of hepatocellular carcinoma. Comparisons may be useful for a differential diagnosis.

Certain other tumors such as a hepatoblastoma or hemangioma of the liver can be mistaken for HCC. A hepatoblastoma is a malignant form of cancer that most commonly affects infants and children. A hemangioma is a non-cancerous (benign) tumor that consists of an overgrowth of blood vessels. Another benign tumor that can occur in the liver is focal nodular hyperplasia. A liver hemangioma and focal nodular hyperplasia are the two most common tumors of the liver.

Diagnosis

Because hepatocellular carcinoma does not cause symptoms early in the disease, getting a prompt diagnosis is difficult. Since there are more effective treatment options the earlier the disease is identified, early diagnosis is very important.

People who have a high risk of developing HCC should enter into a surveillance program. This program involves studying the liver through an ultrasound examination every six months. During an ultrasound, reflected sound waves are used to create an image of internal organs or structures such as the liver. Such a program is the only effective way to detect and diagnose HCC in a timely fashion, so that curative treatment options can still be used. People with hepatitis B or cirrhosis from any cause should be enrolled in such a surveillance program. (Patients with hepatitis C who do not have cirrhosis are not typically screened for liver cancer).

Doctors may then recommend advanced imaging techniques such as computed tomography (CT) scan or magnetic resonance imaging (MRI) to try and confirm a diagnosis of HCC. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of specific organs and bodily tissues.

People who are not in a surveillance program may be diagnosed because they have liver disease and doctors discover that they have rising alpha-fetoprotein levels. This protein occurs in high levels in developing fetuses, but is usually not seen in high levels in children or adults. High levels of this protein might indicate liver cancer, especially in people who have underlying liver disease. Doctors will usually order a CT scan or MRI to try and detect the presence of liver cancer.

Sometimes, doctors may need to take a tiny sample of liver tissue to be studied under a microscope to confirm a diagnosis of HCC. This is called a liver biopsy. During a biopsy, a needed is passed through the skin to take a tiny sample of affected liver tissue. There is a risk of false negatives, so careful surveillance with imaging tests is still recommended even if the biopsy is negative. There is also a risk of “tumor seeding” during a biopsy, where cancer cells spread to neighboring tissues, in this instance, along the path the biopsy needle travels. Because of these risks, liver biopsy is not routinely performed for people with typical imaging features of HCC.

Standard Therapies

Treatment

Hepatocellular carcinoma usually occurs in people who have an underlying liver disease or liver dysfunction. Treatment may require the coordinated efforts of a team of specialists. Specialists who diagnose and treat cancer (oncologists), specialists who diagnose and treat liver disorders (hepatologists), specialists who use ionizing radiation to treat cancer (radiation oncologists), specialists who use minimally-invasive, image-guide technologies to diagnose and treat cancer (interventional radiologists), transplant surgeons, and surgeons who specialize in the liver and gall bladder and bile ducts (hepatobiliary surgeon), and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment. Psychosocial support for the entire family is essential as well.

Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease stage; tumor size; the presence or absence of certain symptoms; whether the disease has spread (metastasized) to other areas of the body; how well or poorly the liver is functioning overall; an individual’s age and general health; and/or other elements. Decisions concerning the use of surgery, radiation, specific drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.

Because people with HCC usually have an underlying liver condition, that condition needs to be monitored and treated as well. The underlying liver condition will greatly impact the longer-term survival of an affected individual.

Physicians will stage HCC as part of developing a treatment plan. Cancer staging is used to determine how far cancer has progressed in a person and where it is located within the body. The most commonly used staging system is the Barcelona Cancer of the Liver staging system which takes into consideration liver function, daily performance ability and the size and number of liver tumors.

If HCC is found early enough and the underlying liver condition hasn’t compromised liver function, a patient may be eligible for surgical removal (resection) of the tumor. Surgical resection is best undertaken by a hepatobiliary surgeon because they are experienced with liver surgery. Additionally, some people with small tumors may be candidates for a liver transplant.

If surgery or a transplant is not possible, affected individuals may undergo radiofrequency ablation or microwave ablation. Radiofrequency ablation is a procedure in which a small needle is inserted into the tumor and used to deliver high-frequency alternating current (radiofrequency waves) that destroys (ablates) affected tissue. Microwave ablation is a procedure that destroys tumors in the liver by using heat generated f by microwave energy.

Some people may undergo transarterial chemoembolization or TACE. This procedure involves injecting a chemotherapeutic drug into the main artery of the liver to cut of the blood supply to the tumor or tumors. Generally, TACE is used for people with multifocal disease (cancer in many areas of the liver), preserved liver function, and good performance status without of cancer outside the liver (extra-hepatic) or in the portal vein, the large veins that carries blood from the intestines to the liver. Performance status refers to a person’s ability to perform normal daily activities.

Some people who have cancer that has spread outside of the liver or affects the portal or hepatic veins, have good performance status and preserved liver function, have benefited with treatment with a drug called sorafenib. In 2007, the U.S. Food and Drug Administration (FDA) approved sorafenib for hepatocellular carcinoma that could not be treated by surgery (unresectable).

Investigational Therapies

Some physicians may recommend that a person with HCC join a clinical trial, especially if their disease seems resistant to standard treatment options. As of March 2017, there are clinical trials on different aspects of sorafenib treatment for HCC, a modified version of sorafenib called regerafenib, a drug that is in the same class as sorafenib called tivantinib, other drug therapies, and techniques to improve surgical options or liver transplantation for HCC. Immunotherapies, which are therapies that enhance the body’s immune system to help fight disease, are also being studied.

Some researchers are using focused external beam radiation to destroy (ablate) liver tumors that cannot be destroyed through other ablative techniques. With external beam radiotherapy, focused radiation laser beams are directed by a machine to the liver to destroy cancer cells.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Years Published

2017

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